Bioorthogonal bond-cleavage reactions have evolved into powerful tools for chemical biology, representing a promising strategy for achieving controlled release of molecules under physiologically relevant conditions, even in living organisms. Since their discovery, significant efforts have been invested in the development and understanding of the underlying chemistries to enhance the click-to-release performance, biocompatibility, and stability of bioorthogonal tools. In this review, we aim to provide a concise overview of click-triggered bioorthogonal bond-cleavage reactions, with an emphasis on the mechanisms and characteristics of the most commonly applied click-to-release chemistries.

Non-coding RNAs (ncRNAs) are functional RNA molecules that do not code for proteins. Among these, circular RNAs (circRNAs) represent a recently identified class of endogenous ncRNAs with a pivotal role in gene regulation, alongside short ncRNAs (e.g., microRNAs or miRNAs) and long non-coding RNAs (lncRNAs). CircRNAs are characterized by their single-stranded, covalently closed circular structure, which lacks polyadenylated tails and 5'-3' ends. This unique circular conformation makes them resistant to exonuclease degradation, rendering them more stable than linear RNAs, such as mRNAs in human blood cells, which highlights their potential as biomarkers. Both linear and circular RNAs are derived from pre-mRNA precursors. However, while linear RNAs are produced through conventional splicing, circRNAs are primarily formed through a process known as reverse splicing. CircRNAs can be categorized into five basic types: exon circRNAs, circular intronic RNAs, exon–intron circRNAs, intergenic circRNAs, and fusion circRNAs. These molecules have been shown to significantly influence key hallmarks of cancer, including sustained growth signaling, proliferation, angiogenesis, resistance to apoptosis, unlimited replicative potential, and metastasis. This article will delve into the biogenesis and functions of circRNAs, explore their roles in cancer, and discuss their potential applications as therapeutic options and diagnostic biomarkers.Graphical

The increasing use of pesticides necessitates the development of innovative analytical methods to regulate environmental impacts and ensure food safety. Aptamer-based sensors hold great promise for pesticide detection owing to their superior selectivity, stability, repeatability, and regenerative capabilities. Integrated with nanomaterials, aptasensors have demonstrated enhanced sensitivity for detecting a broad range of pesticides. This study first introduces the aptamer binding mechanism and presents the fundamental concept and justification for selecting aptamer over other biorecognition molecules. It then provides a comprehensive review of recent advancements and applications of various types of aptasensors for targeted pesticide detection, including electrochemical, fluorescent, colorimetric, electrochemiluminescent, and surface-enhanced Raman scattering (SERS) aptasensors. Additionally, it offers a comparative analysis of different aptasensors by evaluating their strengths and limitations. Finally, this review discusses strategies, such as advanced Systemic Evolution of Ligands by Exponential Enrichment (SELEX) technique, self-assembled monolayers (SAMs), and the use of antifouling agents to improve the aptamer’s selectivity, signal-to-noise ratio, and mitigate nonspecific adsorption challenges. These developments are essential for creating highly sensitive and selective aptasensors, facilitating their practical use in environmental monitoring and food safety.

In the last decade, the use of bioorthogonal chemistry toward medical applications has increased tremendously. Besides being useful for the production of pharmaceuticals, the efficient, nontoxic reactions open possibilities for the development of therapies that rely on in vivo chemistry between two bioorthogonal components. Here we discuss the latest developments in bioorthogonal chemistry, with a focus on their use in living organisms, the translation from model systems to humans, and the challenges encountered during preclinical development. We aim to provide the reader a broad presentation of the current state of the art and demonstrate the numerous possibilities that bioorthogonal reactions have for clinical use, now and in the near future.

Research on heterocyclic compounds is an area of continuous focus, capturing the interest of both synthetic and natural product chemists. Indazoles are one of the rare heterocycles that are available in nature. Indazole and its derivatives are one of the most important classes of heterocycles in pharmacological molecules. The structurally different indazole motifs, with impressive bioactivity, have drawn increasing attention from medicinal chemists in recent years for the continuous development of novel drug moieties. Thus, knowledge of the biological activities and synthetic pathways of indazole scaffolds is essential to enhancing further developments in the number of indazole-based lead molecules. The goal of the present review is to highlight information on the biological properties of some existing indazole-based drugs and activities of novel bioactive indazole compounds in clinical trails, with specific attention to the most recent advances in various synthetic strategies towards indazole and its derivatives over the past 7 years (2017–2024). Moreover, we discuss the substrate tolerance and mechanistic insights for most of the summarized synthetic protocols.Graphical

Graphdiyne (GDY) is a new variant of nano-carbon material with excellent chemical, physical and electronic properties. It has attracted wide attention from researchers and industrialists for its extensive role in the fields of optics, electronics, bio-medics and energy. The unique arrangement of sp-sp2 carbon atoms, linear acetylenic linkages, uniform pores and highly conjugated structure offer numerous potentials for further exploration of GDY materials. However, since the material is at its infancy, not much understanding is available regarding its properties, growth mechanism and future applications. Therefore, in this review, readers are guided through a brief discussion on GDY's properties, different synthesis procedures with a special focus on surface functionalization and a list of applications for GDY. The review also critically analyses the advantages and disadvantages of each synthesis route and emphasizes the future scope of the material.

Indole, a ubiquitous and structurally versatile aromatic compound, has emerged as a key player in the synthesis of diverse heterocyclic frameworks via cycloaddition reactions. These reactions are completely atom-economical and, hence, are considered as green reactions. This review article provides a comprehensive overview of the pivotal role played by indole in the construction of complex and biologically relevant heterocyclic compounds. Here we explore the chemistry of indole-based cycloadditions, highlighting their synthetic utility in accessing a wide array of heterocyclic architectures, including cyclohepta[b]indoles, tetrahydrocarbazoles, tetrahydroindolo[3,2-c]quinoline, and indolines, among others. Additionally, we discuss the mechanistic insights that underpin these transformations, emphasizing the strategic importance of indole as a building block. The content of this article will certainly encourage the readers to explore more work in this area.

Computational organic chemistry has become a valuable tool in the field of bioorthogonal chemistry, offering insights and aiding in the progression of this branch of chemistry. In this review, I present an overview of computational work in this field, including an exploration of both the primary computational analysis methods used and their application in the main areas of bioorthogonal chemistry: (3 + 2) and [4 + 2] cycloadditions. In the context of (3 + 2) cycloadditions, detailed studies of electronic effects have informed the evolution of cycloalkyne/1,3-dipole cycloadditions. Through computational techniques, researchers have found ways to adjust the electronic structure via hyperconjugation to enhance reactions without compromising stability. For [4 + 2] cycloadditions, methods such as distortion/interaction analysis and energy decomposition analysis have been beneficial, leading to the development of bioorthogonal reactants with improved reactivity and the creation of orthogonal reaction pairs. To conclude, I touch upon the emerging fields of cheminformatics and machine learning, which promise to play a role in future reaction discovery and optimization.

Cancer is one of the major noncommunicable diseases, responsible for millions of deaths every year worldwide. Though various cancer detection and treatment modalities are available today, many deaths occur owing to its late-stage detection and metastatic nature. Noninvasive detection using luminescence-based imaging tools is considered one of the promising techniques owing to its low cost, high sensitivity, and brightness. Moreover, these tools are unique and valuable as they can detect even the slightest changes in the cellular microenvironment. To achieve this, a fluorescent probe with strong tumor uptake and high spatial and temporal resolution, especially with highwatersolubility, is highly demanded. Recently, several water-soluble molecules with emission windows in the visible (400-700nm), first near-infrared (NIR-I, 700-1000nm), and second near-infrared (NIR-II, 1000-1700nm) windows have been reported in literature. This review highlights recently reported water-soluble small organic fluorophores/dyes with applications in cancer diagnosis and therapeutics. We systematically highlight and describe the key concepts, structural classes of fluorophores, strategies for imparting water solubility, and applications in cancer therapy and diagnosis, i.e., theragnostics. We discuss examples of water-soluble fluorescent probes based on coumarin, xanthene, boron-dipyrromethene (BODIPY), and cyanine cores. Some other emerging classes of dyes based on carbocyclic and heterocyclic cores are also discussed. Besides, emerging molecular engineering methods to obtain such fluorophores are discussed. Finally, the opportunities and challenges in this research area are also delineated.